Currently there are no vaccines available for the prevention of disease caused by group B N. meningitidis strains, which accounts for 30-80% of meningococcal disease. Outer membrane vesicle vaccines are known to confer protection in humans but the bactericidal activity is strain-specific. My mentors (Moe et al.) recently showed that sequential immunization with outer membrane vesicle vaccines prepared from three heterologous meningococcal strains, each with different capsular groups, PorA serosubtypes, and PorB serotypes, elicits broadly protective bactericidal antibodies against genetically diverse meningococcal strains, in part by eliciting antibodies to conserved proteins that typically are poorly immunogenic. I propose to develop improved vesicle vaccines by: (1) over-expressing certain highly conserved antigens, such as Neisserial surface protein A (NspA), that have been shown to elicit protective antibodies during sequential immunization, and (2) eliminating antigens that elicit antibodies that do not confer protection, or variable antigens that elicit strain-specific antibodies.